A bicistronic adenoviral vector carrying cytosine deaminase and GM-CSF genes significantly improves antitumor immunity and overall survival in colon cancer

dc.authorid0000-0003-1631-5739
dc.authorid0000-0002-7289-6251
dc.authorid0000-0003-0060-259X
dc.contributor.authorAkbulut, Hakan
dc.contributor.authorÇöleri, Arzu
dc.contributor.authorŞahin, Günce
dc.contributor.authorTang, Yucheng
dc.contributor.authorDeisseroth, Albert
dc.date.accessioned2021-06-23T19:49:38Z
dc.date.available2021-06-23T19:49:38Z
dc.date.issued2018
dc.departmentBAİBÜ, Fen Edebiyat Fakültesi, Biyoloji Bölümüen_US
dc.descriptionAnnual Meeting of the American-Association-for-Cancer-Research (AACR) -- APR 14-18, 2018 -- Chicago, ILen_US
dc.description.abstractBackground: Combination of cytotoxic treatments with immunotherapeutic agents seem more efficacious than using either strategy alone. Oncolytic viral vectors carrying immunostimulatory genes like GM-CSF have emerged as treatment options in various tumors. Previously, we have shown that combination of suicide gene therapy either with GM-CSF or vector-induced dendritic cells has significant anti-tumor efficacy. In the current study, we aimed to combine the cytotoxic effect of the suicide gene cytosine deaminase and the immunostimulatory effect of granulocyte macrophage colony stimulating factor in a single vector construct. Methods: We have constructed a bicistronic adenoviral vector carrying cytosine deaminase (CD) and granulocyte macrophage-colony stimulating factor (GM-CSF) genes combined with an IRES element and driven by CMV promoter (Ad-CMV-CDiresGMCSF). We tested the in vitro efficacy of the vector in various tumor cell lines and in a mouse model of colon cancer. Results: Our bicistronic vector Ad-CMV-CDiresGMCSF showed significant in-vitro cytotoxic effects on tumor cell lines similar to the vector carrying CD gene alone when 5-FC added. Likewise, the GM-CSF producing efficacy of the bicistronic vector was comparable to the vector carrying GM-CSF gene alone. In the syngeneic colon cancer model, the bicistronic vector carrying CD and GM-CSF genes yielded significant tumor shrinkage and overall survival when compared to the control suicide vector carrying CD gene alone. Accordingly, anti-tumor immune response parameters including CTL assay and immune cell infiltration of tumor tissue were significantly improved in the Ad-CMV-CDiresGMCSF vector treated group (p<0.01). Conclusions: The Ad-CMV-CDiresGMCSF vector construct suggests a potential for the treatment of established tumors by inducing significant tumor killing and tumor-specific immune response.en_US
dc.description.sponsorshipAmer Assoc Canc Resen_US
dc.identifier.doi10.1158/1538-7445.AM2018-5911
dc.identifier.issn0008-5472
dc.identifier.issn1538-7445
dc.identifier.issue13en_US
dc.identifier.urihttps://doi.org/10.1158/1538-7445.AM2018-5911
dc.identifier.urihttps://hdl.handle.net/20.500.12491/9568
dc.identifier.volume78en_US
dc.identifier.wosWOS:000468819505325en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.institutionauthorŞahin, Günce
dc.language.isoenen_US
dc.publisherAmer Assoc Cancer Researchen_US
dc.relation.ispartofCancer Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCytosine Deaminaseen_US
dc.subjectGM-CSF Genes
dc.subjectBicistronic Adenoviral Vector
dc.subjectColon Cancer
dc.titleA bicistronic adenoviral vector carrying cytosine deaminase and GM-CSF genes significantly improves antitumor immunity and overall survival in colon canceren_US
dc.typeArticleen_US

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